Alpha-Melanocyte-Stimulating Hormone (α-MSH)
A 13 amino acid peptide derived from proopiomelanocortin (POMC) that stimulates melanin production in melanocytes through MC1R activation. α-MSH also acts on MC3R and MC4R to regulate appetite and energy balance. Afamelanotide and setmelanotide are synthetic analogues of α-MSH.
Technical Context
α-MSH (Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2, 13 aa) is derived from POMC processing (the same precursor that produces ACTH and beta-endorphin — ACTH contains the α-MSH sequence within its first 13 residues). The His-Phe-Arg-Trp tetrapeptide (positions 6-9) is the core pharmacophore for melanocortin receptor activation. Afamelanotide (Scenesse) is [Nle4, D-Phe7]-α-MSH — an α-MSH analogue with norleucine replacing methionine at position 4 (preventing oxidation) and D-phenylalanine replacing L-phenylalanine at position 7 (improving stability and MC1R selectivity). Setmelanotide uses a cyclic peptide design for MC4R selectivity. The melanocortin system represents one of the most extensively drugged peptide receptor families.